Basic research in biological rhythms can be related to affective illness with respect to (1) the involvement of disturbed circadian rhythms (24 hour cycles) in the pathophysiology of the illness and (2) the inherent cyclicity of the illness (itself a type of biological rhythm). Indications of circadian rhythm involvement in the illness come from clinical observations: depressive symptoms exhibit a daily rhythm with worsening in the morning and improvement in the evening; the timing of the sleep-wake cycle and the sleep-wake fraction are abnormal. Previous clinical investigations of many physiological and biochemical variables have shown that circadian rhythm phases, amplitudes and waveforms are abnormal in some depressives. This project is designed to further investigate the behavior of circadian rhythms and manic-depressive cycles in affective patients studied naturalistically and longitudinally. Continuous aroung-the-clock measurements of wrist motor activity, rectal temperature and sleep EEG are obtained using ambulatory electronic monitoring devices. In some instances circadian rhythms in plasma hormones are measured for 1-3 days via indwelling venous catheters. Results to date indicate the following circadian rhythm abnormalities in depressed patients: (1) phase instability with both normal and advanced phase positions of the rectal temperature rhythm on different nights in the same patient, (2) abnormal double-length, 48-hour sleep-wake cycles at the time of the switch from depression to mania in rapid cycling manic-depressives, (3) absence of the thyroid stimulating hormone (TSH) circadian rhythm, and failure of sleep deprivation to stimulate TSH secretion in rapid cycling patients. These last findings are particularly interesting in light of other evidence that thyroid impairment may predispose to the rapid cycling form of the illness. From continuous long-term monitoring of rapid cycling patients we have found (1) additional cases where tricyclic antidepressants markedly accelerated or induced rapid cycling, (2) fundamental independence of manic-depressive and menstrual cycles.